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Neurosci Lett. 2002 Apr 5;322(2):131-3.

The amyloid-beta peptide binds to cyclin B1 and increases human cyclin-dependent kinase-1 activity.

Author information

1
Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, London, UK. nmilton@rfc.ucl.ac.uk

Abstract

The pathological features of Alzheimer's disease include deposition of amyloid-beta (Abeta) containing plaques and increases in the expression of cyclin-dependent kinase (CDK) enzymes. Chemical inhibition of CDKs prevents the neurotoxicity of the Abeta peptide. The activity of these kinases requires the binding of a cyclin component to the catalytic enzyme component. This study characterizes direct interactions between Abeta and cyclin B1. Abeta fragments containing the cytotoxic 31-35 region could inhibit biotinylated Abeta binding to cyclin B1. The same cytotoxic Abeta fragments all increased CDK-1 phosphorylation of known substrates in a cell free system. The CDK-1 inhibitor olomoucine prevented the cytotoxicity of Abeta 31-35 containing peptides in differentiated human teratocarcinoma cell line, Ntera 2/cl-D1 (NT-2) neurons. These direct interactions between cyclin B1 and Abeta provide potential mechanisms for the cytotoxicity of the Abeta peptide.

PMID:
11958860
[Indexed for MEDLINE]

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